19-36099478-G-C

Variant names:

• chr19-36099478-G-C
• rs757558839
• NM_001083961.2:c.2600G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001083961.2(WDR62):​c.2600G>C​(p.Arg867Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.36

Genes affected

WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.2600G>C	p.Arg867Pro	missense_variant	Exon 22 of 32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.2600G>C	p.Arg867Pro	missense_variant	Exon 22 of 32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0063	.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.23	T;T
Sift4G	Benign	0.28	T;T
Polyphen		1.0	D;D
Vest4		0.60
MutPred		0.55		Loss of MoRF binding (P = 0.0221);Loss of MoRF binding (P = 0.0221);
MVP		0.75
MPC		1.0
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.61
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757558839; hg19: chr19-36590380;